論文

査読有り
2015年3月

Identification of Genetic Loci Affecting the Severity of Symptoms of Hirschsprung Disease in Rats Carrying Ednrb(sl) Mutations by Quantitative Trait Locus Analysis

PLOS ONE
  • Jieping Huang
  • ,
  • Ruihua Dang
  • ,
  • Daisuke Torigoe
  • ,
  • Chuzhao Lei
  • ,
  • Xianyong Lan
  • ,
  • Hong Chen
  • ,
  • Nobuya Sasaki
  • ,
  • Jinxi Wang
  • ,
  • Takashi Agui

10
3
開始ページ
e0122068
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0122068
出版者・発行元
PUBLIC LIBRARY SCIENCE

Hirschsprung's disease (HSCR) is a congenital disease in neonates characterized by the absence of the enteric ganglia in a variable length of the distal colon. This disease results from multiple genetic interactions that modulate the ability of enteric neural crest cells to populate developing gut. We previously reported that three rat strains with different backgrounds (susceptible AGH-Ednrb(sl/sl), resistant F344-Ednrb(sl/sl), and LEH-Ednrb(sl/sl)) but the same null mutation of Ednrb show varying severity degrees of aganglionosis. This finding suggests that strain-specific genetic factors affect the severity of HSCR. Consistent with this finding, a quantitative trait locus (QTL) for the severity of HSCR on chromosome (Chr) 2 was identified using an F-2 intercross between AGH and F344 strains. In the present study, we performed QTL analysis using an F-2 intercross between the susceptible AGH and resistant LEH strains to identify the modifier/resistant loci for HSCR in Ednrb-deficient rats. A significant locus affecting the severity of HSCR was also detected within the Chr 2 region. These findings strongly suggest that a modifier gene of aganglionosis exists on Chr 2. In addition, two potentially causative SNPs (or mutations) were detected upstream of a known HSCR susceptibility gene, Gdnf. These SNPs were possibly responsible for the varied length of gut affected by aganglionosis.

Web of Science ® 被引用回数 : 4

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0122068
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25790447
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000351425400209&DestApp=WOS_CPL
ID情報
  • DOI : 10.1371/journal.pone.0122068
  • ISSN : 1932-6203
  • PubMed ID : 25790447
  • Web of Science ID : WOS:000351425400209

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